肝细胞癌中高OATP1B3表达增强索拉菲尼疗效的机制研究  

Mechanism study of high OATP1B3 expression in hepatocellular carcinoma to enhance the efficacy of Sorafenib

作　　者：林毅豪 胡育海[1,2,3] 郑洲 张翔[1] LIN Yihao;HU Yuhai;ZHENG Zhou;ZHANG Xiang(Department of Hepatobiliary and Pancreatic Surgery,The First Affiliated Hospital of Fujian Medical University,Fuzhou,Fujian,China,350005;Institute of Abdominal Surgery,The First Affiliated Hospital of Fujian Medical University,Fuzhou,Fujian,China,350005;National Regional Medical Center,The First Affiliated Hospital of Fujian Medical University,Fuzhou,Fujian,China,350005)

机构地区：[1]福建医科大学附属第一医院肝胆胰外科,福建福州350005 [2]福建医科大学附属第一医院腹部外科研究所,福建福州350005 [3]福建医科大学附属第一医院国家区域医疗中心,福建福州350005

出　　处：《分子诊断与治疗杂志》2024年第10期1982-1986,共5页Journal of Molecular Diagnostics and Therapy

基　　金：福建省自然科学基金资助项目(2020J05252)。

摘　　要：目的探究肝细胞癌中高OATP1B3表达对索拉菲尼疗效的增强效果及相关机制。方法选取2016年1月至2018年12月福建医科大学附属第一医院收治的48例肝癌患者的病理组织样本为研究材料,观察OATP1B3在肝癌组织和距肿瘤边缘2 cm的癌旁组织中的表达情况、OATP1B3表达对服用索拉非尼患者生存期的影响。并通过转染肿瘤细胞,探究OATP1B3高表达对转染的Hep-1细胞的影响、与OATP1B3表达有关的相关信号通路分析以及索拉菲尼处理OATP1B3高表达肿瘤细胞的生物行为影响。结果48例肝癌患者的癌组织中的OATP1B3的mRNA表达、蛋白表达水平和免疫组化评分低于癌旁组织,差异有统计学意义(P<0.05)。转染OATP1B3的Hep-1细胞增殖能力、迁移和侵袭能力均低于阴性对照细胞,差异有统计学意义(P<0.05)。转染OATP1B3的Hep-1细胞中N-cadherin、Vimentin、β-catenin、Bcl2干细胞样中CD33、OCT4、NANOG和SOX-2的表达均下调,E-cadherin、BAX、C-caspase3表达上调,且细胞凋亡率高于阴性对照细胞。经索拉菲尼处理后,OATP1B3高表达的肿瘤细胞生长和活性均下降;服用索拉非尼的肝癌患者中,高OATP1B3表达的患者生存期显著延长;且以OATP1B3表达水平可作为预测服用索拉非尼患者生存期的独立危险因素(P<0.05)。结论肝细胞癌组织中的OATP1B3高表达状态可有效增强索拉菲尼的疗效,抑制癌症发展,为相关治疗方案优化提供了一定的理论依据。Objective To explore the enhancement effect of high OATP1B3 expression in hepatocellular carcinoma(HCC)on sorafenib and its related mechanisms.Methods The study selected 48 liver cancer patients admitted to the First Affiliated Hospital of Fujian Medical University from January 2016 to December 2018 as research subjects.The aim was to observe the expression of OATP1B3 in liver cancer tissue and adjacent tissues 2 cm from the tumor edge,and to investigate the impact of OATP1B3 expression on the survival of patients receiving sorafenib treatment.High expression of OATP1B3 in transfected Hep-1 cells was examined,along with an analysis of the relevant signaling pathways involved in the expression of OATP1B3,and biological behavior effects of sorafenib on OATP1B3 high expression tumor cells were explored through transfection of tumor cells.Results The mRNA expression,protein expression level and immunohistochemical score of OATP1B3 in cancer tissues of 48 patients with liver cancer were lower than those in adjacent tissues,and the differences were statistically significant(P<0.05).The proliferation,migration and invasion abilities of Hep-1 cells transfected with OATP1B3 were lower than those of negative control cells,and the difference was statistically significant(P<0.05).In Hep-1 cells transfected with OATP1B3,the expressions of N-cadherin,Vimentin,β-catenin,CD33,OCT4,NANOG and SOX-2 in Bcl2 stem cell-like cells were down-regulated,while the expressions of E-cadherin,BAX and C-caspase3 were up-regulated.The apoptosis rate was higher than that of negative control cells.After treatment with sorafenib,the growth and activity of tumor cells with high OATP1B3 expression were decreased.In HCC patients treated with sorafenib,the survival time of patients with high OATP1B3 expression was significantly prolonged.The expression level of OATP1B3 could be used as an independent risk factor for predicting the survival time of patients taking sorafenib(P<0.05).Conclusion The high expression of OATP1B3 in hepatocellular carcinoma

关 键 词：肝细胞癌 OATP1B3基因 索拉菲尼 机制研究 

分 类 号：R735.7[医药卫生—肿瘤]